A microphysiological system to investigate the pressure dependent filtration at an artificial glomerular kidney barrier

Abstract

Chronic kidney disease (CKD) is a global health problem that affects around 11 to 13% of the world’s population and more than 18% of European citizens. Characteristic syndromes of CKD during all stages of the disease are proteinuria and ongoing glomerular dysfunction caused by cellular damages at the glomerular filtration barrier. While some rare cases of the disease are correlated to genetic depositions the majority of cases are caused by diabetes, glomerulosclerosis, high blood pressure and glomerulonephritis. Thus, recapitulating the interplay of high blood pressure and changes at the glomerular filtration barrier in vitro seems an adequate way to mimic CKD. Here we present a microphysiological system of the glomerular filter that is capable to simulate high blood pressure at the glomerular filtration barrier in vitro. It consists of a closed loop microfluidic circuit with an integrated pneumatically driven heart like micro pump that constantly circulates the cell culture media at the blood site of the glomerular barrier. The ThinCert™ insert could be reversibly integrated into a holder system that ensures the correct position of the insert within the microfluidic circuit. By using different modulations of the integrated pneumatic micro pump different physiological and pathophysiological conditions e.g. hypertonic stress, like in CKD, could be applied. The influence of hypertonic conditions on the filtration above the barrier was studied by changes of TEER values and measurement of the flux of fluorescent labelled albumin through the cellular barrier.

Keywords

• glomerular filtration barrier
• chronic kidney disease
• glomerulus on chip
• hypertonia on chip